H-89 is a protein kinase inhibitor with greatest effect on protein kinase A (PKA).[2] H-89, derived from H-8 (N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide),[3] was initially believed to act specifically as an inhibitor of PKA,[4] being 30 times more potent than H-8 at inhibiting PKA and 10 times less potent at inhibiting protein kinase G. It achieves this through competitive inhibition of the adenosine triphosphate (ATP) site on the PKA catalytic subunit.[5] However, subsequent work has suggested a variety of additional effects such as inhibition of other protein kinases (IC50 values of 80, 120, 135, 270, 2600 and 2800 nM for S6K1, MSK1, PKA, ROCKII, PKBα and MAPKAP-K1b respectively),[6] and direct inhibition of various potassium currents.[7]
In addition to its use in studying mechanisms of cell signalling, H-89 has also been used experimentally in vivo. H-89 has been shown to increase the threshold and latency of pentylenetetrazol-induced seizures [8] and decrease morphine withdrawal symptoms in mice.[9]
^Marunaka, Yoshinori; Niisato, Naomi (2003). "H89, an inhibitor of protein kinase A (PKA), stimulates Na+ transport by translocating an epithelial Na+ channel (ENaC) in fetal rat alveolar type II epithelium". Biochemical Pharmacology. 66 (6): 1083–9. doi:10.1016/S0006-2952(03)00456-8. PMID12963496.
^Hidaka, H.; Inagaki, M.; Kawamoto, S.; Sasaki, Y. (1984-10-09). "Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C". Biochemistry. 23 (21): 5036–5041. doi:10.1021/bi00316a032. ISSN0006-2960. PMID6238627.
^Murray, A. J. (2008). "Pharmacological PKA Inhibition: All May Not Be What It Seems". Science Signaling. 1 (22): re4. doi:10.1126/scisignal.122re4. PMID18523239.